Declining mental health in the elderly represents an enormous public health problem. Much remains to be learned about Alzheimer's-type dementia (AD or Primary Degenerative Dementia) and there currently are no effective treatments. Depression in the elderly is also a major problem, and difficulties exist concerning differential diagnosis between depression and early dementia. The objective of this proposal is to utilize the positron emission tomogrpahy-11C-deoxyglucose technique (PET-CDG) in conjunction with certain psychoactive drug probes to study the brain dysfunction correlates of AD and geriatric depression. We have previously used PET III and 18F-DG to study regional brain metabolism in aging and AD. We reported significant diminutions in regional rates of glucose utilization which correlate well with degree of cognitive impairment. Assuming that the brain's response to psycho-active drugs is altered differentially in AD and depression, we now hypothesize that administration of certain drugs will enhance the utility of PET for studying the brain-function correlates of declining mental health in aging, and for increasing its potential utility for differential diagnosis. To test this hypothesis we propose to study 3 subject groups (AD, geriatric depression, and elderely normal controls) and 4 drug interventions (amphetamine, naloxone, physostigmine and placebo). Thirty subjects (aged 55-85) will be assigned to each drug study, 10 from each subject group (total N = 120). All subjects will receive extensive clinical/diagnostic evaluations, including medical/neurological exams, CT, psychiatric evaluation and cognitive/neuropsychological testing. PET 6-CDG scans will be obtained both before and after a single dose of the study medication. We hypothesize that amphetamine may produce widespread increases in brain metabolism and may be best for differentiating depression; naloxone may have primary effects on limbic and cortical areas; and physostigmine may primarily affect cholinergic areas and be best for differentiating AD. The results of this project will increase our knowledge about AD and depression, and may ultimately lead to improved diagnosis and treatment.